Determinants of weight, psychological status, food contemplation and lifestyle changes in patients with obesity during the COVID-19 lockdown: a nationwide survey using multiple correspondence analysis.

INTRODUCTION: The corona virus disease 2019 (COVID-19) pandemic forced most of the Italian population into lockdown from 11 March to 18 May 2020. A nationwide survey of Italian Clinical Nutrition and Dietetic Services (Obesity Centers or OCs) was carried out to assess the impact of lockdown restrictions on the physical and mental wellbeing of patients with obesity (PWO) who had follow-up appointments postponed due to lockdown restrictions and to compare determinants of weight gain before and after the pandemic. METHODS: We designed a structured 77-item questionnaire covering employment status, diet, physical activity and psychological aspects, that was disseminated through follow-up calls and online between 2 May and 25 June 2020. Data were analyzed by multiple correspondence analysis (MCA) and multiple linear regression. RESULTS: A total of 1,232 PWO from 26 OCs completed the questionnaires (72% female, mean age 50.2 ± 14.2 years; mean BMI 34.7 ± 7.6 kg/m2; 41% obesity class II to III). During the lockdown, 48.8% gained, 27.1% lost, while the remainder (24.1%) maintained their weight. The mean weight change was +2.3 ± 4.8 kg (in weight gainers: +4.0 ± 2.4 kg; +4.2% ± 5.4%). Approximately 37% of participants experienced increased emotional difficulties, mostly fear and dissatisfaction. Sixty-one percent reduced their physical activity (PA) and 55% experienced a change in sleep quality/quantity. The lack of online contact (37.5%) with the OC during lockdown strongly correlated with weight gain (p < 0.001). Using MCA, two main clusters were identified: those with unchanged or even improved lifestyles during lockdown (Cluster 1) and those with worse lifestyles during the same time (Cluster 2). The latter includes unemployed people experiencing depression, boredom, dissatisfaction and increased food contemplation and weight gain. Within Cluster 2, homemakers reported gaining weight and experiencing anger due to home confinement. CONCLUSIONS: Among Italian PWO, work status, emotional dysregulation, and lack of online communication with OCs were determinants of weight gain during the lockdown period.

The Effect of beta-blockade on objectively measured physical fitness in patients with abdominal aortic aneurysms--A blinded interventional study.

BACKGROUND: Perioperative beta-blockade is widely used, especially before vascular surgery; however, its impact on exercise performance assessed using cardiopulmonary exercise testing (CPET) in this group is unknown. We hypothesized that beta-blocker therapy would significantly improve CPET-derived physical fitness in this group. METHODS: We recruited patients with abdominal aortic aneurysms (AAA) of <5.5 cm under surveillance. All patients underwent CPET on and off beta-blockers. Patients routinely prescribed beta-blockers underwent a first CPET on medication. Beta-blockers were stopped for one week before a second CPET. Patients not routinely taking beta-blockers underwent the first CPET off treatment, then performed a second CPET after commencement of bisoprolol for at least 48 h. Oxygen uptake (.VO2) at estimated lactate threshold and .VO2 at peak were primary outcome variables. A linear mixed-effects model was fitted to investigate any difference in adjusted CPET variables on and off beta-blockers. RESULTS: Forty-eight patients completed the study. No difference was observed in .VO2 at estimated lactate threshold and .VO2 at peak; however, a significant decrease in .VE/.VCO2 at estimated lactate threshold and peak, an increase in workload at estimated lactate threshold., O2 pulse and heart rate both at estimated lactate threshold and peak was found with beta-blockers. Patients taking beta-blockers routinely (chronic group) had worse exercise performance (lower .VO2 ). CONCLUSIONS: Beta blockade has a significant impact on CPET-derived exercise performance, albeit without changing .VO2 at estimated lactate threshold and.VO2 at peak. This supports performance of preoperative CPET on or off beta-blockers depending on local perioperative practice. CLINICAL TRIAL REGISTRATION: NCT 02106286.

Comparison of oxygen uptake during arm or leg cardiopulmonary exercise testing in vascular surgery patients and control subjects.

BACKGROUND: Cardiopulmonary exercise testing by cycle ergometry (CPET(leg)) is an established assessment tool of perioperative physical fitness. CPET utilizing arm ergometry (CPET(arm)) is an attractive alternative in patients with lower limb dysfunction. We aimed to determine whether oxygen uptake obtained by CPET(leg) could be predicted by using CPET(arm) alone and whether CPET(arm) could be used in perioperative risk stratification. METHODS: Subjects underwent CPET(arm) and CPET(leg). To evaluate the ability of VO2 obtained from CPET(arm) to predict VO2 from CPET(leg), we calculated prediction intervals (PIs) at lactate threshold θ(L) and peak exercise in both groups. Receiver operating characteristic (ROC) curves were used to risk stratify patients into high and low categories based on published criteria. RESULTS: We recruited 20 vascular surgery patients (17 males and three females) and 20 healthy volunteers (10 males and 10 females). In both groups, PIs for at and peak were wider than clinically acceptable (patient group - VO2 at θ(L) CPET(arm) ranged from 55% to 108% of CPET(leg) and from 54% to 105% at peak; healthy volunteers - 37-77% and 41-79%, respectively). The area under the ROC for CPET(arm) VO2 in patients was 0.84 [95% confidence interval (CI): 0.66, 1.0] at θ(L), and 0.76 (95% CI: 0.54, 0.99) at peak. CONCLUSIONS: Although a relationship exists between VO2 values for CPET(arm) and CPET(leg), this is insufficient for accurate prediction using CPET(arm) alone. This however does not necessarily preclude the use of CPET(arm) in perioperative risk stratification.

[Phylogenetic analysis of the family of p53].

A relationship between the functional significance of individual amino acid residues of the p53 protein, their positions in the protein structure, and the mode of evolution of the codons corresponding to these residues has been established. A phylogenetic analysis of the coding sequences of the gene of p53 from 32 vertebrate species has been performed. It was found that those codons undergo selection that affect the efficiency of binding of protein p53 as a transcription factor. It was shown that the frequency of occurrence of generative mutations maintaining the normal function of the protein in conservative codons differs statistically significantly from the frequency of occurrence in the same codons of mutations with the effects of loss and acquisition of the function, and the negatively dominant effect. The phylogenetic analysis and molecular dynamics modeling made it possible to obtain evidence for the functional significance of the G245 residue for which the appearance of the binding site for Zn2+ in the case of the substitution G245G has previously been proposed.

Primate-rodent 3H-MPTP binding differences, and biotransformation of MPTP to a reactive intermediate in vitro.

Specific binding of 3H-MPTP to brain homogenates is displaced predominantly by MAO-A inhibitor clorgyline in rat, and by MAO-B inhibitor deprenyl in monkey. A covalently bound metabolite is formed by MAO-B in vitro from MPTP, through a reaction almost completely inhibited by physiological concentrations of glutathione and significantly reduced by other sulfhydryl containing compounds. The difference in binding site pharmacological properties may account for the relative resistance of rat to the neurotoxic effect produced by MPTP in primates. The glutathione-prevented metabolic conversion to a reactive intermediate may be important for the mechanism of MPTP neurotoxicity and relevant to idiopathic Parkinson's disease.

The substitutions G245C and G245D in the Zn(2+)-binding pocket of the p53 protein result in differences of conformational flexibility of the DNA-binding domain.

Transcription activation of the proapoptotic target genes is a means by which the p53 protein implements its function of tumor suppression. Zn(2+) is a known regulator of p53 binding to the target genes. We have previously obtained an evidence that amino acid substitutions in the p53 Zn(2+)-binding pocket can presumably exert an influence on Zn(2+) position in the Zn(2+)-p53 complex and thereby affect p53 binding to DNA. With these background considerations, our aim was to estimate the effect of the putative changes in the Zn(2+) position in its binding pocket due to the G245C and G245D substitutions on the conformation of the p53 DNA-binding motif. Statistical analysis of the molecular dynamics (MD) trajectories of the mutant p53-Zn(2+) complexes was used to detect significant deviations in conformation of the mutant p53 forms. MD simulations demonstrated that (1) the two substitutions in the Zn(2+)-binding pocket caused changes in the conformation of the p53 DNA-binding motif, as compared with the wild-type (WT) p53; (2) binding of Zn(2+) to the p53 mutant forms reduced the effect of the substitutions on conformational change; and (3) Zn(2+) binding in the normal position compensated the effect of the mutations on the conformation in comparison to the altered Zn(2+) position.

A reactive metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is formed in rat brain in vitro by type B monoamine oxidase.

The formation of a reactive intermediate in the oxidative metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that can covalently bind to monoamine oxidase or other cellular macromolecules has been postulated by several authors. We report here direct in vitro evidence that MPTP is converted by monoamine oxidase, predominantly type B, to a reactive metabolite, which binds irreversibly to proteins in rat brain. Rat brain homogenates were incubated at 37 degrees C with 1-[methyl-3H]MPTP and the perchloric acid precipitates were washed exhaustively with organic solvents and counted for radioactivity. The amount of recovered radioactivity was enzyme-related: it was time- and temperature-dependent and did not occur with preboiled tissue. This metabolic activity required oxygen; it was concentrated in the crude mitochondrial fraction and varied in different brain regions. Pargyline and deprenyl prevented the radioactivity binding, whereas clorgyline was less potent, indicating that monoamine oxidase, predominantly of type B, is the enzyme responsible for the production of the reactive metabolite. Glutathione and, to a lesser extent, cysteine and dithiothreitol, but not ascorbic acid, inhibited the irreversible protein binding, suggesting that sulfhydryl groups may react with the metabolite possibly leading to SH-conjugates. 1-Methyl-4-phenyl-2,3-dihydropyridinium increased the irreversible protein binding, indicating that the reactive metabolite of MPTP may not be identified as the dihydropyridinium compound. This chemically reactive intermediate might play a role in MPTP neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: correspondence of its binding sites to monoamine oxidase in rat brain, and inhibition of dopamine oxidative deamination in vivo and in vitro.

A saturable, specific, high-affinity binding site for [3H]1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was found in rat brain homogenates. The CNS regional distribution, the subcellular fractionation, and the displacement by pargyline, clorgyline, and deprenyl suggest that this binding site may correspond to monoamine oxidase. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine inhibited the oxidative deamination of dopamine, both in vivo and in vitro. Striatal levels of 3,4-dihydroxyphenylacetic acid were significantly reduced shortly after intravenous administration, and returned to normal values after a few hours. The in vitro formation of 3,4-dihydroxyphenylacetic acid from dopamine was inhibited by concentrations of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine comparable to those of pargyline.

Decrease of thyroid hormones in patients with familial hypercholesterolemia during dextran sulphate low-density lipoprotein apheresis.

Removal of low-density lipoproteins from plasma by dextran sulfate adsorption (DSA) in FH patients entails a decrease in plasma levels of thyroid hormones (-28.5% and -18.7%, respectively, for T3 and T4). This suggests that FH patients have a greater than normal fraction of thyroid hormones bound to lipoproteins, due to their expanded lipoprotein pool.

The effect of atenolol on the growth hormone response to growth hormone-releasing hormone in obese children.

We have evaluated the effect of acute administration of atenolol, a selective beta-adrenergic antagonist, on the GH response to GHRH in nine obese children and in eight age-matched controls. The GH response to GHRH (1-29, 1 microgram/kg iv), evaluated both as the GH peak and as integrated area under the curve, was significantly lower in the obese children than in the controls. Pretreatment with atenolol (50 or 100 mg orally in subjects with body weight less than or greater than 40 kg, respectively, administered 120 min before the GHRH injection) significantly increased the GH response to GHRH in the obese subjects, such that their mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were similar to those of the control children after GHRH. Also in control children, atenolol caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were significantly higher in the controls than in the obese children given the same treatment. These data show that inhibition of central beta-adrenergic receptors counteracts the blunted GH response to GHRH present in the obese children. In view of the alleged mechanism of action of beta-adrenergic blockade (inhibition of endogenous SRIH release), our data suggest that the somatostatinergic system is intact in obesity, and that the suppressed GH secretion is due to other causes.

Secretion of growth hormone releasing hormone in obese children.

We have evaluated baseline and l-dopa-stimulated peripheral growth hormone releasing hormone (pGHRH) secretion in 6 obese pre-pubertal children and in 7 age-matched controls. Baseline pGHRH levels were no different between obese (36.6 +/- 9.8 pg/ml, mean +/- SE) and control children (40.6 +/- 10.1 pg/ml). Administration of l-dopa (500 mg po) caused a significant increase of pGHRH levels in both the obese (65.3 +/- 19.8 pg/ml, p less than 0.05) and the control children (84.1 +/- 10.0 pg/ml, p less than 0.003). Mean peak pGHRH levels after l-dopa were not significantly different between the two groups, whereas mean peak GH levels were significantly lower (p less than 0.05) in the obese (7.9 +/- 1.9 ng/ml) than in the control children (20.5 +/- 4.9 ng/ml). We conclude that despite reduced GH secretion, obese children have normal baseline and l-dopa stimulated pGHRH levels.

Effects of sheep alpha s1-casein CC, CD and DD genotypes on milk composition and cheesemaking properties.

The effects of sheep alpha s1-casein CC, CD and DD genotypes on milk composition and cheese yield were studied. Processed bulk milk was collected from three groups of 15 ewes, carrying alpha s1-casein CC, CD and DD genotypes. CC milk was higher in casein content than CD or DD milk (+3.5 and +8.6% respectively), and had a higher protein: fat ratio and a smaller casein micelle diameter. In addition, DD milk had a significantly lower alpha s1-casein content. The main differences were in curd formation: CC milk had better renneting properties. Cheesemaking trials, carried out in a pilot plant, showed that CC milk had better cheesemaking characteristics than DD milk, while CD milk was intermediate. Both 1 d old and fully ripened cheeses had different fat: dry matter ratios and alpha s1-I-casein electrophoretic mobilities: these were lower for DD cheese. As a consequence, these genotypes could be considered as markers of milk and/or cheese quality.

The effect of galanin on baseline and GHRH-induced growth hormone secretion in obese children.

We have evaluated the effect of the administration of galanin (Gal), a newly identified hypothalamic peptide, on baseline and GHRH-induced GH rise in five obese children and in seven controls. The GH response to GHRH (hpGRF(1-29), 1 microgram/kg i.v.), and to Gal (15 micrograms/kg/h for 1 h), evaluated both as the maximum GH peak and as integrated area under the curve (AUC), was significantly lower in the obese children than in the controls. Simultaneous administration of Gal plus GHRH significantly increased the GH response to GHRH in all the obese subjects, so that their mean peak GH levels and AUC after Gal plus GHRH were similar to those of the control children after GHRH. Also, in control children Gal caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean AUC after Gal plus GHRH were significantly higher in the controls than in the obese children given the same treatment. Our data indicate that obese children have a blunted GH response to Gal, which, however, is able to enhance the GH response to GHRH. This observation strengthens the view that the mechanism of action of Gal involves modulation of endogenous somatostatin (SRIH) release. In addition, similarity between the effects of Gal and pyridostigmine on baseline and GHRH-stimulated GH release in obese children may indicate the existence of a cholinergic link in the action of Gal.